FIGURE 4.

Inhibitory assay of Vpr mutants with hit and potent derivatives. Growth of wild-type and mutant Vpr-expressing yeasts at 36 h in the presence or absence of compounds. Wild-type and L68A were representative of standard and weakened Vpr cell cycle arrest activity, respectively. Hit compound 3 was no longer potent against most of the mutants shown here, but their resistance was overcome by 5 and vipirinin. Notably, S28A was resistant to all inhibitors, whereas Q65A had good growth arrest activity in yeast, although reported otherwise in mammalian cells. In this assay, the hit compound and derivatives were used at their optimum concentrations (final concentrations are 3, 100 μm; 5, 25 μm; vipirinin, 10 μm). H, hydrophobic residues. The error bars denote S.D.